title: Cobalt-alkyne complexes with imidazoline ligands as estrogenic carriers: synthesis and pharmacological investigations.
abstract: We synthesized (4R,5S)/(4S,5R)-N-propargyl-4,5-bis(2-chloro-4-methoxy/hydroxyphenyl)-2-imidazolines (1 and 2) as estrogenic carriers for the dicobalthexacarbonyl fragment. The OH-substituted ligand 2 and its related complex 2-Co(2)(CO)(6) showed estrogenic activity in a transcriptional assay in ERalpha-containing MCF-7-2a cells. The cytotoxicity against breast cancer cell lines was more pronounced for the related O-methyl derivative 1-Co(2)(CO)(6). Further pharmacological investigations were performed on the cellular uptake into MCF-7 and MDA-MB-231 cells, the ability of binding to DNA, and the inactivation by HSA.
authors.affiliation: Institute of Pharmacy, Freie Universitat Berlin, Konigin Luise Strasse 2 + 4, 14195 Berlin, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Schlenk
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D047628:Estrogen Receptor alpha / Q000378:metabolism; D004967:Estrogens / Q000737:chemistry*; D006801:Humans; D048288:Imidazolines / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D000480:Alkynes; D047628:Estrogen Receptor alpha; D004967:Estrogens; D048288:Imidazolines; D008024:Ligands; D009942:Organometallic Compounds; D003035:Cobalt; D004247:DNA